News | April 2019

Recent Developments

FDA Approves Dupixent for Moderate to Severe AD in Adolescents

The FDA has approved expanded use of Dupixent from Regeneron Pharmaceuticals, Inc. and Sanofi SA to include patients aged 12 through 17 whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Dupixent (dupilumab) can be used with or without topical corticosteroids.

The FDA evaluated the Dupixent application under Priority Review. Dupixent was also granted Breakthrough Therapy designation by the FDA for inadequately controlled moderate to severe atopic dermatitis in adolescents.

In the pivotal Phase 3 trial evaluating Dupixent monotherapy in adolescent patients with uncontrolled moderate to severe atopic dermatitis, the safety and efficacy were generally consistent with that previously seen in adult studies. At 16 weeks:

• The average improvement in the Eczema Area and Severity Index (EASI) from baseline was approximately 66 percent compared to 24 percent for placebo.

• More than 10 times as many patients had clear or almost clear skin with Dupixent compared to placebo: 24 percent of patients who received Dupixent achieved clear or almost clear skin compared to 2 percent with placebo, as measured by an Investigator’s Global Assessment score of 0 or 1, the primary endpoint.

• Over five times as many patients saw overall disease improvement of at least 75 percent with Dupixent compared to placebo: 42 percent of patients who received Dupixent achieved 75 percent or greater skin improvement compared to 8 percent with placebo, as measured by EASI-75.

• More than seven times as many patients experienced significantly reduced itch with Dupixent compared to placebo: 37 percent of patients who received Dupixent achieved a clinically meaningful improvement in itch of at least four points on the Peak Pruritus Numerical Rating Scale compared to 5 percent with placebo.

The safety profile of Dupixent in the adolescent trial was similar to the safety profile from trials in adults with atopic dermatitis, and consistent through 52 weeks.

“This is a really big deal because there are so many adolescents and children with eczema,” says Emma Guttman-Yassky MD, PhD, Vice Chair for Research in the Department of Dermatology and Director of the Center for Excellence in Eczema at Mount Sinai Hospital in New York City. “For many of these patients, topicals aren’t enough and phototherapy isn’t feasible.”

“Dupixent is a very safe treatment, and we hope in the future its use will be expanded to include early childhood.” Dr. Guttman-Yassky’s research and clinical trials helped lead to FDA approval in adults and adolescents.

Biopelle Launches Emepelle

Biopelle, Inc. has launched Emepelle, the first and only clinically proven skincare line that safely and effectively helps address Estrogen Deficient Skin (EDS). Emepelle features MEP Technology, a patented, specifically designed ingredient designed to non-hormonally restore the natural function of Estrogen Deficient Skin. The Emepelle product line consists of a serum and a night cream.

As women age, estrogen levels naturally decline. Although women may notice skin dryness or changes to the condition of their skin as they get older, they likely do not make the correlation with declining estrogen levels, Biopelle says. Low estrogen results in skin dryness, atrophy, wrinkling and thinning. In the first five years of menopause, low estrogen levels lead to a 30 percent loss of the skin’s collagen and a subsequent 2.1 percent loss each year thereafter.

AAD Announces 2019 Election Results

The votes have been counted in the 2019 AAD Election, and the following candidates will take office at the conclusion of the 2020 Annual Meeting.

The 2019 Academy election also included proposed bylaws amendments, which must be approved by a two-thirds majority of the total votes cast to be adopted.

Voters approved an amendment to create a new International Associate category of membership and re-align other international membership categories to address inconsistencies in the current application process and align international categories with US categories.

Ortho Dermatologics is accepting applications for its 2019 Aspire Higher scholarship program, which will award $90,000 total in scholarships to nine students who have been treated for a dermatologic condition.

Students can apply for the Aspire Higher scholarship through April 26, 2019, and winners will be announced on July 10, 2019.

To apply, students must share an essay about their experience of living with a dermatologic condition, as well as the role that a dermatologist, physician assistant, or nurse practitioner played in helping treat them. To learn more about the scholarship and to see stories from previous winners, visit AspireHigherScholarships.com.

Sciton Introduces JOULE X and More at ASLMS

Sciton Inc. unveiled JOULE X and other new offerings at the annual American Society for Laser Medicine and Surgery (ASLMS) Meeting in Denver.

An upgrade to the JOULE platform, JOULE X is the company’s latest multi-device platform. It works with HALO, diVa, Resurfacing Perfected, Allura, and BBL (BroadBand Light) and features three distinct delivery modes: arm, fiber, and broadband light.

BTL Adds Emsculpt Applicator for Arms, Thighs, Calves

BTL rolled out out a small Emsculpt applicator to treat arms, thighs and calves at the annual meeting of the ASLMS in Denver.

Until now, there were only protocols for the abdominals and buttocks.

Biofrontera Reports Positive Phase 3 Results with Ameluz

Results for the primary endpoint of Biofrontera AG’s Phase 3 clinical trial evaluating the safety and efficacy of conventional photodynamic therapy (PDT) with Ameluz and the BF-RhodoLED lamp for the treatment of actinic keratoses (AK) on the extremities as well as the trunk and neck are postive. The study met its primary regulatory endpoint, demonstrating that Ameluz was superior to placebo based on its mean total lesion clearance rate of 86 percent compared, to 33 percent for placebo. These results will be utilized for the filing of a label extension with the European Medicines Agency (EMA) and the US FDA, which Biofrontera plans to submit in the third quarter of 2019.

The multi-center, randomized, double-blind, intra-individual study included 50 patients at six study sites in Germany, each with four to 10 clinically confirmed AK lesions in comparable areas on the right and left side of the extremities and/or trunk/neck. Mild, moderate, and severe actinic keratoses were treated with one or two PDT treatments. The final examination of patients took place three months after the last PDT treatment. The clinical study phase is now followed by a follow-up phase of 12 months after the last PDT, in which recurrence rates and/or numbers of new AKs and skin tumors will be determined.

Are Skin Diseases More Common Than Previously Held?

Skin diseases may be more common than previously believed, according to a new study in the Journal of the European Academy of Dermatology and Venereology that estimates the prevalence of skin diseases outside of the typical medical setting.

Skin diseases are ranked as the fourth most common cause of human illness, but many affected people do not consult a physician. To include people who never or rarely seek medical aid, researchers collected data at the Munich Oktoberfest in Germany where screening examinations were performed randomly on participating visitors. Of the 2,701 individuals in the study, at least one skin abnormality was observed in 1,662 of the participants (64.5 percent). The most common diagnoses were actinic keratosis (26.6 percent), rosacea (25.5 percent), and eczema (11.7 percent). Skin disease incidence increased with age; they were more common in men (72.3 percent) than in women (58.0 percent). Nearly two-thirds of affected participants were unaware of their abnormal skin findings, the study found.

“Information and awareness campaigns are needed to better address this neglected issue and to reduce the global burden of skin diseases,” says senior author Dr. Alexander Zink, of the Technical University of Munich.

CCH is an investigational injectable treatment designed specifically to reduce the appearance of cellulite by disrupting the collagen structure of fibrous septae, which cause dimpling of the skin.

The Phase 2 clinical trial enrolled 375 women aged 18 years or older in the United States who were randomized to receive up to three treatment sessions of CCH (0.84mg/session) or placebo, with each treatment session occurring approximately 21 days apart. Twelve injections were administered into cellulite dimples during each session across an entire treatment area – left or right buttock, or left or right posterior thigh. A significant percentage of trial subjects receiving CCH achieved at least a 1-point improvement of cellulite severity. CCH was well-tolerated in the treated subjects with most adverse events being mild to moderate in severity, and primarily limited to the local injection area (e.g. bruising, pain, nodule, pruritus, erythema, and discoloration).

Dermira’s Investigational AD Drug Performs Well

All three doses of Dermira, Inc.’s lebrikizumab showed greater improvements in the Eczema Area and Severity Index in a Phase 2b dose-ranging study of adults with moderate to severe atopic dermatitis. Shares of Dermira, Inc. skyrocketed in premarket trading after the company announced theresults.

Lebrikizumab is a novel, humanized monoclonal antibody designed to bind IL-13 with high affinity, specifically preventing the formation of the IL-13Rα1/IL-4Rαheterodimer complex, which inhibits downstream signaling. IL-13 is a central pathogenic mediator that drives multiple aspects of the pathophysiology of atopic dermatitis by promoting type 2 inflammation and mediating its effects on tissue, resulting in skin barrier dysfunction, itch, skin thickening and infection.

Following an end-of-phase 2 meeting with FDA, Dermira plans to initiate a Phase 3 clinical development program.

TAKE 5

Excitement about chimeric antigen receptor T-cell (CAR T) therapy began to crescendo in 2011 when initial results from the first treated patients suggested that CAR T therapy had the potential to cure B cell leukemia, and developments have continued at a rapid pace since. There are two CAR T cell therapy products approved for the treatment of certain B cell cancers, and CAR T was named the 2017 Advance of the Year by the American Society of Clinical Oncology. Now newly formed Cabaletta Bio aims to harness this technology to treat and to potentially cure the B-cell mediated autoimmune disease pemphigus vulgaris (PV). Steven Nichtberger, MD co-founder, chief executive officer, and chairman of Cabaletta Bio, talked to Practical Dermatology® magazine.

1. Current Events

Steven Nichtberger, MD: Cabaletta Bio launched out of the University of Pennsylvania with an exclusive licensing deal, two multi-year sponsored research agreements, and a master agreement to partner with Penn to develop a chimeric autoantibody receptor (CAAR) product for PV based on recent proof-of-concept data published in the journal Science by the Penn research team. The company raised $38 million Series A to advance its lead asset, DSG3-CAART. The financing was led by 5AM Ventures. Founding investors Adage Capital Management participated, along with an un-named public equity investor and the University of Pennsylvania.

2. Auspicious beginnings

Dr. Nichtberger: I am a cardiologist but have been involved in the commercial side of the pharma and biotech business for most of my career. For the past eight years I have served as an adjunct professor at the Wharton School of the University of Pennsylvania in health care management and senior fellow in the Vagelos Life Sciences & Management Program. I lead the “capstone class” teaching students how to start, finance, and lead a biotech company. Penn is an extraordinary university that nurtures collaboration across all twelve schools. After the publication of a paper on the use of CAR T technology redirected to specifically address B cell mediated autoimmune diseases, I met the authors who work at Penn Medicine, only a few blocks from my office. We collaborated for quite a while to develop a business plan that would attract investment from professional investors. In May of 2018, the company secured our first financing. We are fortunate to have two outstanding scientific founders. Aimee Payne MD, PhD is an associate professor of dermatology and lead physician in the Autoimmune Blistering Clinic at Penn with longstanding research interests in B cell mediated autoimmunity and PV. Michael Milone, MD, PhD, is an associate professor of pathology and laboratory medicine at Penn. He is also a member of the Center for Cellular Immunotherapies at Penn, and co-inventor of Kymriah®, the CAR-T product developed at Penn. (Tisagenlecleucel (Kymriah®) is approved for acute lymphoblastic leukemia).

3. Why pemphigus vulgaris (PV)

Dr. Nichtberger: Because desmoglein antibodies are necessary to cause PV, we believe it is the best target to prove we can selectively ablate B-cells that are causing a specific autoimmune disease without harming the normal immune system. Despite recent advances, there is an important unmet clinical need. For a patient with the mucosal form of PV, drinking water can feel like swallowing shards of glass, so even a small sore can bring on feelings of post-traumatic stress. Currently, steroids are first line, followed by toxic immunosuppressives. Recently rituximab was approved to treat moderate to severe PV, but even rituximab has substantial risks of hospitalization and substantial costs with chronic therapy required to prevent recurrence and a long history of frequent recurrences despite therapy.

Everybody is using the equivalent of nuclear weapons to treat autoimmune disease. We are using a laser beam with really excellent specificity to treat PV. Based on the preclinical data, we believe that CAAR T therapy can be designed to destroy only the disease-causing B cells without harming adjacent Tcells or normal B cells.

4. A potential one-time cure

Dr. Nichtberger: The desmoglein antibodies have 98-100 percent sensitivity and specificity for the disease. If we eliminate the DSG3 antibodies that cause disease and B cells that make them, it is reasonable to think we will see a clinical improvement. Nobody is currently trying to cure PV; that is our aspiration.

5. Next steps

Dr. Nichtberger: We currently plan to file an investigational new drug application (IND) with the US FFDA to initiate a first clinical study in mucosal PV in the second half of 2019. We are fortunate to have established a strong partnership with the Center for Cellular Immunotherapies at Penn which has substantial experience with advancing cellular therapies into phase 1 clinical trials. If we are able to demonstrate reasonable safety and efficacy in our first clinical study, we would plan to pursue other B cell mediated diseases. Eventually, if the tools in our tool box appear to be effective and reasonably safe in patients, we would consider going into more complicated autoimmune diseases.

Could Moisturization Cut Dementia Risk?

Regular moisturization may cool skin inflammation in older adults and lower disease risk in the process, according to a pilot study published in the Journal of the European Academy of Dermatology and Venereology. In the study, 33 adults aged 58 to 95 applied a lipid-balanced cream all over their bodies twice a day for 30 days. After a month, researchers measured blood levels of three cytokines—interleukin-1 beta, interleukin-6, and tumor necrosis factor (TNF) alpha—that have all been implicated in age-related inflammatory diseases.

Using the cream reduced the amount of all cytokines compared to the levels before using the cream and the levels of similarly aged adults who did not use the cream. Using the cream lowered participants’ cytokine levels to be nearly equivalent with people in their 30s, suggesting that rejuvenating the skin can reverse “inflamm-aging.”

CLOSE UP

With Roy G. Geronemus, MD

There have been widespread concerns about potential risks associated with the repetitive use of general anesthesia in children younger than three, and this has led to questions about the treatment of port wine stains in kids, but anesthesia may not be necessary. Dermatologist Roy Geronemus, MD of Laser & Skin Surgery Center of New York, discussed the results of his recent retrospective study on this issue with Practical Dermatology® magazine.

Why is this topic important to study?

Roy G. Geronemus, MD: We made the observation in clinical practice that port wine stain birthmarks can be safely and effectively treated in early infancy without the need for general anesthesia. This observation is particularly important because of the US FDA warnings regarding multiple exposures to general anesthesia for children under the age of three and the potential impact on neurocognitive development.

Describe the research and your findings.

Dr. Geronemus: This is the largest study to date (n=197) on children under the age of one. Twenty six percent of the babies achieved complete clearing, and 67 percent of the patients had more than 75 percent clearing of their PWS. No scarring or pigmentary change was noted. More complete and rapid clearing than one sees in older patients was noted, supporting the concept of early intervention.

The dramatic response before the children are aware of their birthmarks will be helpful for self esteem and will minimize risks of spontaneous bleeding in future years. (The treatments were performed using the Vbeam Perfecta from Candela without topical or general anesthesia.)

What is the next step?

Dr. Geronemus: Next steps include follow up of these patients with additional treatments beyond the age of one to assess further improvement or clearing.

History of Dermatology Society Award

Frederick C. Gaede, BA, MAS, has received the Samuel J. Zakon Award in the History of Dermatology for his article entitled, “Henry Granger Piffard, MD and His Photogenic Pistol Cartridges.” The Award was announced at the forty-sixth annual meeting of the History of Dermatology Society last month.

Irwin M. Braverman, MD from New Haven, CT, was also recognized. Dr. Braverman presented the lecture, “Wax, Limestone, and Paper: The Foundation of Dermatology.” It focused on imaging of skin diseases and the relation between art and medicine.

The History of Dermatology Society is accepting submissions of articles for consideration for the next Zakon Award. The deadline is November 1. Submissions should be sent to Mark Valentine, MD (mark1105@aol.com).

Verrica PRESENTS Molluscum Data

Verrica Pharmaceuticals, Inc. announced results from two pivotal phase 3 clinical trials of its lead product candidate, VP-102, during the annual meeting of the AAD last month. VP-102 is a proprietary topical drug-device combination in development for the treatment of molluscum contagiosum. Investigator Lawrence Eichenfield, MD discussed the study results.

“Cantharidin hasn’t been formally studied in clinical trials, and there is no FDA-approved agent for treatment of molluscum. The preparation studied offers a consistent concentration of cantharidin: long-term, room temperature stable, in a novel single-use applicator that can be used for dozens of lesions on a single individual. Presently, there is tremendous variation around the country in the ability to get and use cantharadin, due to its uncertain regulatory status, and when obtainable, it is usually compounded in multi-use vials, with variable concentrations and consistencies.”

The studies were large, with more than 520 participants, Dr. Eichenfield notes. “The study drug applied every 21 days until clearance (or a maximum of four applications). Data showed 46 and 54 percent of patients with complete clearance of molluscum at 12 weeks, in a population with a mean of 19-25 lesions and a range up to 184 lesions. The vehicle response was low (13-18 percent complete clearance). The lesion count decreased 69 and 83 percent in the VP-102 groups in the two studies—numbers decreased 19 percent with the vehicle in one study, and increased 20 percent in the other. These were robust statistically.”

Dr. Eichenfield says he welcomes this, “well-designed study that clearly shows the efficacy of cantharadin for molluscum, something to change the Cochrane review of molluscum treatment, which says, ‘we considered the evidence for all outcomes …to be of low quality due to small study size and imprecision.’”

In the study, local reactions, consistent with the effects of cantharadin occurred; most were assessed as mild to moderate. There were no serious AEs in the VP-102 group.

Actress JENNIFER GARNER Talks SUN SAFETY

During the AAD Annual Meeting last month, Neutrogena sponsored an event where actress Jennifer Garner and Doris Day, MD discussed the importance of UV protection. Ms. Garner spoke to Practical Dermatology® about her advocacy for sun safety.

We associate Hollywood with glamour and beauty but don’t always think of sunscreens as part of that. Do you think sunscreen is or could be glamorous?

Jennifer Garner: It used to be that the day you turned 30, your career in Hollywood absolutely ended. But now, if you think about it, we’re all allowed to be glamourous later in life. Look at Halle Berry, Nicole Kidman, and so many amazing women! We’re all moving and grooving—and working—and if you want to be able to do that in Hollywood, your skin needs to look great longer.

Many of the signs of skin aging are due to sun exposure, not genetics! We have control over what we use to make our skin look and feel beautiful. So yes, I do believe it is glamourous to wear sunscreen!

Do you think Hollywood really has moved away from tan as beautiful?

Ms. Garner: I think so! I think we’re going back to more of a natural complexion. My first thought today (when I looked at my legs in this dress) was, “Ooo! I look pale.” My second thought was, “Good; my skin is healthy.” There is a trend heading in that direction for sure, and hopefully Hollywood will influence the rest of the world in that way.

What inspired you to learn about sun safety and make it a passion?

Ms. Garner: I was so lucky; I was inside during most of my teenage years doing theater in the summer, while my friends and sisters were out sunbathing and using baby oil. I would have been with them, had I not decided to stay indoors. Everyone called me Casper, because compared to my sister and friends, I was pale.

I thought I escaped sun damage; I felt it wasn’t going to be a problem I would have, but then suddenly, in my late 30s, I woke up one day and saw the effects of sun damage on my skin. It turns out that I still got quite a bit of sun damage as a young child and it stayed dormant all these years and then, “boom,” it showed up.

You can reverse some of the signs of sun damage by being vigilant about sunscreen, but you really have to be on top of it. So that’s what did it for me, and it really is so simple. Sunscreen became a habit that I just do. You don’t get in a car and start the drive before putting on your seatbelt; you just do it. So just like I buckle myself in a car, when I wake up in the morning and wash my face, brush my teeth and floss, the next step is sunscreen application. Sunscreen is non-negotiable every single day.

What is your “secret weapon” tactic to get someone to use SPF?

Ms. Garner: I tell people younger than me—friends, colleagues, family—that one day you will say, “I should have listened to Jen earlier!” I tell them, “I care about you and I know you can’t imagine it now, but you are damaging your skin and you will care later in life.” They never get upset with me for telling them to wear sunscreen because they see what it can do for their skin to keep it beautiful and healthy. It really matters, every day. So I keep telling them to do it!

Correction

In the September 2018 Aesthetics Management column, “Oral Fixation: Dietary Supplements for Skin Support” by Matthew Zirwas, MD, the recommended dosing for minoxidil 2% solution was listed incorrectly. It should have read: Patients concerned with hair loss should put 0.25 teaspoon of minoxidil 2% solution into 2 cups (approx 500ml) of water, then take 1 teaspoon a day.